EP2205960A1

EP2205960A1 - Method and device for the exact reflectometric determination of the optical density of the macular pigment xanthophyll on the ocular fundus without interference by stray light

Info

Publication number: EP2205960A1
Application number: EP08802732A
Authority: EP
Inventors: Dietrich Schweitzer; Martin Hammer; Thomas Mohr
Original assignee: Carl Zeiss Meditec AG
Current assignee: Carl Zeiss Meditec AG
Priority date: 2007-10-02
Filing date: 2008-10-01
Publication date: 2010-07-14
Also published as: WO2009046912A1; DE102007047300A1

Abstract

1. A method and device for the exact reflectometric determination of the optical density of the macular pigment xanthophyll on the ocular fundus without interference by stray light, particularly by individual light scattering in the front eye media 2.1 The aim of the invention is to be able to reflectometrically determine also the optical density of the macular pigment xanthophyll on the ocular fundus without interference by stray light, particularly individually interfering stray light of the front eye media. 2.2 According to the invention, in addition to measuring the reflection light from illuminated regions of the ocular fundus, the ocular fundus is only partially illuminated and the intensity of the stray light is measured from the non-illuminated region. Said measurement value serves as a corrective variable for calculating the optical density of the macular pigment. 2.3 The invention is used in the field of ophthalmology.

Description

Description of the invention

METHOD AND DEVICE FOR EXACTLY REFLECTOMETRIC DETERMINATION

THE OPTICAL DENSITY OF THE MAKULAPIGMENT XANTHOPHYLL ON THE EYE BACKGROUND WITHOUT INFLUENCE THROUGH BURNS

The invention relates to a method and a device for measuring the reflection light from the ocular fundus, the optical density of the macular pigment xanthophyll on the ocular fundus from the logarithmic quotient of the values of a compensation function and the reflection light measured in the macular region in monochromatic illumination of the ocular fundus with light in the absorption maximum of To calculate xanthophyll very exactly.

The macular pigment xanthophyll protects the macula, the area of the sharpest vision, from damage due to the absorption of the high-energy blue light. B. as a result of the formation of free radicals. At the same time, the macular pigment, which mainly contains the hydroxy-substituted ß-carotenes lutein and zeaxantine, acts as a radical scavenger. A low optical density of the macular pigment is a risk factor for the onset of age-related macular degeneration. Since lutein and zeaxantine are not formed by the body, but must be ingested with food, it is necessary to determine the individual level of optical density of the macular pigment, in order to detect a possible hazard and derive any necessary supplementation of lutein and zeaxantine.

With the invention, the optical density of Makulapigments is to be determined very accurately and free of interfering light, which arises in layers that are upstream of the object to be examined, especially the ocular fundus. These scattering effects distorting the disturbing and the reflectometric measurement results, especially as a result of the eye lens, increase with age, so that with increasing age of the patient also the known determination of the optical density of the macular pigment xanthophyll on the ocular fundus results from the logarithmic quotient of the values said compensating function and the reflection light measured in the macula region is more affected by the scattering effects.

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An exact determination of the optical density of the macular pigment xanthophyll, however, is important for the decision on the necessity and proof of the success of the aforementioned supplementation with lutein and zeaxantine, which is to be detected as an increase in the optical density of the macular pigment.

It is known (for example, from DE 101 29 652 A1, the entire disclosure of which is referred to below) to illuminate the fundus with light of a wavelength range, optimally having a wavelength in which the macular pigment xanthophyll absorbs to a maximum extent , From the light intensity, which is measurable outside the macular area, in which no xanthophyll is present, a compensation function (shading function) is determined. This takes into account the natural vignetting and illumination differences due to the adjustment of the measuring system to the eye. To calculate the optical density of the macular pigment, the quotient of the calculated value of the compensation function and the measured intensity value of the reflection light from the illuminated fundus is calculated for each pixel in the region of the macula. The compensation function virtually indicates the reflected light that would be reflected from the fundus in the area of the macula if no xanthophyll were present. The logarithm of these quotients corresponds to the double optical density of the macular pigment (douple density) 2ODχ of xanthophyll:

compensation

2OD _x = log (1)

However, trials have shown that increasing scattering S in the anterior ocular media, caused by age-related ocular media haze, results in a reduced xanthophyll optical density reading. This is shown by adding an equal value S for the scattering in numerator and denominator of equation (1):

2OD _x = log ^{1 A → lül + S.} (2) As the value S increases, the logarithm decreases and, for the case Unequal, Imess ^<<: S, in which the quotient tends towards the value 1, reaches the value zero, so that the optical density of the macular pigment, due to the scattering of the light in the anterior ocular media is too small for all reflectometric procedures.

If the light scattering in the eye lens shows a strong wavelength dependency, the optical density of the macular pigment is also overstated as the scattering increases with the 2-wavelength fluorescence method. The age dependence of the xanthophyll optical density determined by means of Raman fluorescence measurements is essentially determined by the weakening of the excitation light as a result of the increasing scattering in the eye lens with age.

Various solutions are known for detecting the disturbing fluorescence light of the anterior ocular media in measurements of the fluorescence at the ocular fundus. In DE 10 2005 058 185 A1, the spectra are detected simultaneously or successively in the case of confocal illumination of the ocular fundus as well as non-confocal illumination and detection. With confocal illumination, the measuring light from the ocular fundus and the interfering extraneous light, but with non-confocal illumination, only the external light is detected. The subtraction of both radiations yields only the light to be measured by the fundus. This solution is based on a confocal system, which is, however, only in laser scanning devices, but not based on the principle of fundus-based ophthalmoscopes.

It has also been proposed (DE 10 2007 025 425.5), disturbing fluorescent light z. As the anterior ocular media simultaneously with measurements of fundus fluorescence to capture. For this purpose, part of the observed fundus is not excited to fluoresce. The light measured by this region is assigned to the fluorescence that is excited by the light reflected from the fundus in the anterior segment of the eye, and this light is then subtracted from all other pixels. However, this method is not suitable for obtaining undisturbed fluorescence or reflection light for each fundus area, since one area is always hidden, in practical applications in particular the macular area, which has just to be evaluated for determining the optical density of the macular pigment. In addition, it is known (DE 10 2004 042 198 Al) to eliminate disturbing fluorescence or scattered light of the anterior ocular media to combine the confocal illumination and detection principle with the principle of Aperturblendenteilung, which, however, in turn, requires a confocal laser scanning system which only one single point is illuminated.

The invention is based on the object, even without compelling prerequisite of a laser scanning device, to be able to determine the optical density of the macular pigment xanthophyll on the ocular fundus without being influenced by stray light, in particular individually interfering stray light of the anterior ocular media, by refiectometric analysis. In particular, the invention should also be applicable in fundus cameras.

According to the invention, in addition to the known measurement of the reflection light from illuminated areas of the fundus in a previous or subsequent step (possibly also simultaneously) the fundus is only partially illuminated and the intensity of the light is measured as stray light from a non-illuminated area of the fundus. From each pixel of light from the illuminated fundus, the stray light measured in the non-illuminated area of the fundus is subtracted. The compensation function is determined from the measured values corrected in each case for the stray light component from selected regions of the ocular fundus outside the macula. The optical density of the macular pigment can be calculated according to equation (3): With:

U _k -: values of the corrected compensation function, calculated from the values of the reflection light of areas outside the macula, reduced by the values of the disturbance light, which were obtained from a non-illuminated area of the fundus with partial illumination of the fundus, and

I _m u: values of the reflection light in the macula area with illumination of the macular area, reduced by the values of the stray light, that of an unlit one Area of the fundus with partial illumination of the fundus.

In an ophthalmoscope known per se, a field stop is inserted into the illumination beam path for incident light detection, through which the observable ocular fundus is only partially illuminated, and a further insertable field stop is provided in the measurement beam path, which field is only used for the light to be measured as disturbance light from the unlit part of the field Ocular fundus is permeable, so that in this case only the remitted light from the specially unlighted (by the illumination in the illumination beam path) shadowed part of the ocular fundus is measured.

In this way, in the reflectometric determination of the optical density of the macular pigment xanthophyll, the influence of stray light, in particular of individual light scattering in the anterior ocular media, is eliminated.

In the subclaims further advantageous embodiments of the invention are listed.

The invention can be used for all opthalmological devices based on the fundus camera principle for the reflectometric examination of the ocular fundus and does not necessarily require a confocal laser scanning principle. A further, applicative improvement is obtained if the position of the field stop in the illumination beam path can preferably be adapted automatically to the defective vision of the patient.

A further improvement of the measurement may result if a corresponding filter in the observation beam path is provided for the suppression of interference light caused by autofluorescence of ocular tissue.

To further increase the accuracy of the compensation function can be checked by their determination in several areas of the fundus or even corrected.

It is also advantageous if the distribution of the optical density of the macular pigment is evaluated with regard to its shape. The invention will be explained in more detail below with reference to an ophthalmologic device shown in the drawing for the reflectometric determination of the optical density of the macaque lap polyanthophyll as an exemplary embodiment.

Show it:

Fig. 1: Illumination of the fundus with a circular field and measurement of the light from the entire illuminated area.

FIG. 2: Illustration of an annular illumination field on the fundus of the eye centrally around the macula, wherein the area of the macula of approximately 2 degrees is not illuminated, but only light from this area is measured.

3 shows a schematic 3D representation of the optical density of the macular pigment.

FIGS. 1 and 2 are based on the basic structure of a known ophthalmoscope with an illumination beam path 1 and a measurement beam path 2, which is used for eye examination.

A light source 3 with limited spectral range in the wavelength range of the absorption of the macular pigment xanthophyll is imaged in a known manner in the illumination beam path 1 via lenses 4 and 5 in the annular aperture Ap 1. The aperture diaphragm AP 1 is imaged via a lens 6, a perforated mirror 7 and a further lens 8 in the aperture plane of the eye as an aperture diaphragm image AP 1 ', so that with the eye lens 9 a homogeneous illumination of the fundus 10 is realized. In Fig. 1 is located for example in the focal plane of the lens 5, a circular field stop FB 1 through which the fundus 10 via the lens 6, the hole mirror 7, the lens 8 and the lens 9 in a field FB 1 'preferably centrally around the Macula is illuminated in the spectral region in which xanthophyll absorbs. A arranged in the focal plane of lens 8 in the measuring beam 2 circular field stop FB 2 allows for imaging by lenses 1 1 and 12, the radiation detection by a detector 13 of the entire circularly illuminated field of the fundus 10th

In Fig. 2, in contrast to Fig. 1 in the focal plane of the lens 5, an annular field stop FB 3 is arranged, which in the illumination beam path 1 via the lenses 5 and 6, the hole mirror 7, the lens 8 and the eye lens 9, an illuminated annular field FB 3 ^' on the fundus 10 with an outer diameter of preferably 2.4 PD (diameter papilla) and an inner diameter of preferably 1.2 PD generated. It is essential that the field diaphragm 3 is designed so that the area of the macula, in which the optical density of the macular pigment xanthophyll is to be determined, is not illuminated in this case. The illumination of the fundus 10 may also be as described in Fig. 1, but the macular area remains unlit.

In the measurement beam path 2, for example in the focal plane of a lens 8, a circular field stop FB 4 is arranged, which after the imaging of the fundus 10 via the eye lens 9 and the lens 8 only for a self-unlit field (macular) with a diameter of preferably 0.4 PD is permeable. A circular aperture diaphragm AP 2, preferably in the focal plane of the lens 1 1, whose aperture diaphragm image AP 2 'is imaged on the eye lens 9, prevents in a known manner the detection of illumination light which is reflected on the anterior ocular media such as the eye lens 9. The light imaged by a lens 12 onto the measuring field of a detector 13 from the normally unilluminated central field around the macula of the fundus 10 is mainly light which has been scattered several times in the anterior ocular media, predominantly in the ophthalmic lens 9. From the ocular fundus 10 diffusely reflected light entering the aperture diaphragm AP 2 'directly or by scattering in the eye lens 9 is also detected. Also multiple scattered fluorescent light, which was excited by the illumination in the eye lens 9 is also detected by this measurement. However, this fluorescent light is much weaker than the scattered illumination light.

To correct the measurement light for the calculation of the optical density of the macular pigment xanthophyll, the radiation which was measured at all pixels in the case of circular illumination of the ocular fundus 10 (see Fig. 1) subtracts that radiation which is emitted when the ocular fundus 10 is illuminated annularly the non-illuminated field (in the present embodiment, the macular region of the fundus 10) was measured (see Fig. 2). This light, which is measured on the basis of the field stops FB 3 and FB 4 in the illumination or measuring beam path 1, 2 from the non-illuminated field of the fundus 10 (macular region) corresponds to the From the thus corrected values of the reflection light with complete illumination of the ocular fundus, the compensation function preferably becomes the annular region between 1.2 PD and 2.4 PD in a known manner certainly. This subtracts the scatter proportion in the numerator and denominator that interferes with equation (2). The optical density of the macular pigment is then calculated according to equation (3): With:

I _Ak '. Values of the corrected compensation function, calculated from the values of the reflection light from areas outside the macula, reduced by the values of the disturbance light, which were obtained from an unlighted area of the fundus with partial illumination of the fundus, and

I _n *: values of the reflection light in the macular area with illumination also of the macular area, reduced by the values of the stray light, which were obtained from an unlighted area of the fundus with partial illumination of the fundus.

The field diaphragms FB 3 and FB 4 can each advantageously be arranged in the illumination or measuring beam path 1, 2 to be pivoted in and out (not shown in the drawing for reasons of clarity). It is also possible (also not shown in the figures) to execute the field apertures FB 2 and FB 4 as a single aperture with variable free diameter.

Accurate determination of the stray light requires sharp imaging of the shading apertures on the patient's retina. Thus, an adaptation to an existing defective vision of the patient is required. For this purpose, the shading diaphragm is preferably positioned in the illumination beam path to the conjugate plane of the patient retina. Preferably, a possibility for the automatic determination of the refractive error eg by means of autofocus is available. With the particular Value of the individual ametropia, the shading aperture is automatically adjusted to the defective vision.

Another solution for the suppression of autofluorescence

Distortion light is to introduce into the observation beam a filter which blocks the light not originating from the fluorescence of the macular pigment. For the

Example of Xanthophyll would be a filter suitable, which light above 490nm

Wavelength suppressed. For example, this filter could be near the position of

Field stop FB 2 or aperture AP 2 be provided. Alternatively, at

Realization of the detector 13 are read by a color camera only the blue pixels.

It has been shown to be involved in dietary supplementation of substances that

Accumulate fundus pigment such as lutein and zeaxantine, can also accumulate in the area outside the macula. In such a case, the evaluation area for the compensation function would be to increase or a correction is required.

The correction can preferably take place in that the optical density at the edge of

Evaluation area with an optical density value far outside the

Evaluation area is compared.

It is preferred in an unstructured, annular area far outside the

Macula determines an averaged value of optical density and with an averaged one

Value of the optical density compared at the edge of the circular macula evaluation area.

If the optical density at the edge of the evaluation area is higher than the reference value far outside the macula, the optical density of the fundus pigment will increase by the value of

Difference between the two values increased.

For this purpose, the values obtained in the arrangement according to FIG. 1 are charged accordingly.

A distribution of the macular pigment obtained as a result of the entire calculation is in

Fig. 3 ideally shown in 3D.

In the border area, it can also be a change in shape of the original circular

Area come; up to a very rugged contour. For an improved

Diagnosis may thus benefit the calculation and display of a measure of the deviation from the circular structure. Preferably, this measure is determined in the range of average optical density to minimize noise effects. This measure can be determined, for example, from the relationship between the enclosed area and the total length of the outer contour and compared with a normatively determined limit value in order to achieve a clarification of the diagnostic statement.

Due to illness, the optical density of the fundus pigment xanthophyll in the 3 D representation can deviate from a rotationally symmetric distribution with a certain variance. The maximum of the optical density can occur, for example, at the edge of the distribution function. Furthermore, a very locally limited but very high optical density can occur. Thus, the display of a measure of the deviation from the rotationally symmetric structure is advantageous for the improved diagnosis. For the assessment of a local increase, a measure is calculated from the central moment of the second order (corresponding to the variance) and displayed to the user. For the assessment of the deviation from a rotationally symmetric distribution, a measure of the central third-order moment (corresponding to the skewness) is calculated and displayed to the user.

This measure can be compared with a normatively determined limit and serve to clarify the diagnosis statement.

In order to avoid distortions of the result due to a low signal-to-noise ratio, the determination of a statistical measure for the evaluation of the signal-to-noise ratio is advantageous. Preferably, in the structureless regions outside the macula (which are also used for the determination of the compensation function) a measure of the signal-to-noise ratio of the xanthophyll optical density is determined and compared with a normatively determined limit and serves the user to qualify the made Measurement..

The invention is not limited to the application for determining the optical density by means of the 1-wavelength reflection method, but also improves the accuracy in 2- or multi-wavelength methods for reflectometric xanthophyll determination at the fundus.

Claims

Patent claims

1. Method for the precise reflectometric determination of the optical density of the macular pigment xanthophyll at the fundus of the eye, in which the optical density of the macular pigment present in the macular area is determined from the logarithmic quotient of the values of a compensation function and the reflected light measured in the macular area when the fundus of the eye is monochromatically illuminated with light, if possible at the absorption maximum of xanthophyll is calculated, characterized in that in addition to measuring the reflected light from illuminated areas of the fundus of the eye, the fundus of the eye is only partially illuminated and the intensity of the light is measured as stray light from a non-illuminated area of the fundus of the eye, that from each pixel of the light from the illuminated fundus of the eye that the measured stray light in the unilluminated area of the fundus of the eye is subtracted and that the compensation function is calculated from the measured values corrected for the stray light component from selected areas of the fundus of the eye outside the macula.

2. The method according to claim 1, characterized in that the macular area in which the optical density of the macular pigment xanthophyll is to be determined is selected as the unilluminated area of the fundus of the eye.

3. The method according to claim 1, characterized in that the fundus of the eye is illuminated in a ring to measure the stray light.

4. The method according to claim 1, characterized in that an average value is formed from the measured stray light and that this stray light mean value is subtracted from the light of each pixel from the illuminated fundus of the eye.

5. The method according to claim 2, characterized in that the partial illumination of the fundus of the eye to detect the stray light is carried out at a safety distance from the macular area in order to exclude the measurement of reflected light from the illuminated fundus of the eye when measuring stray light in the unilluminated macular area.

6. The method according to claim 1, characterized in that the calculation of the simple optical density of the xanthophyll according to the relationship

1 . /.

OD _x = -log ' Ak

2 /„,, is done with:

I _Ak : Values of the corrected compensation function, calculated from the values of the reflected light from areas outside the macula, reduced by the values of the stray light obtained from an unilluminated area of the fundus with partial illumination of the fundus, and

I _m k: Values of the reflected light in the macular area when the macular area is also illuminated, reduced by the values of the stray light that were obtained from an unilluminated area of the fundus of the eye with partial illumination of the fundus of the eye.

7. The method according to claim 1, characterized in that the measurement of the intensity of the light as stray light from a non-illuminated area of the fundus of the eye is carried out in a preceding or subsequent step for measuring the reflected light from illuminated areas of the fundus of the eye.

8. The method according to claim 1, characterized in that the fundus of the eye is only partially illuminated for measuring the reflected light from illuminated areas of the fundus of the eye and at the same time the intensity of the light is measured as stray light from a non-illuminated area of the fundus of the eye.

9. The method according to claim 8, characterized in that a circular area with a diameter of 0.4 PD is selected as the unilluminated area of the fundus of the eye.

10. Device for the precise reflectometric determination of the optical density of the macular pigment xanthophyll at the fundus of the eye using an ophthalmoscope, for example a fundus camera, through whose illumination beam path (1) the fundus (10) of the eye is completely illuminated via a first field stop (FB 1) and in whose measuring beam path ( 2) a second field diaphragm (FB 2) is arranged for a detector (13), which is transparent to all of the light remitted by the eye, characterized in that an insertable third field diaphragm (FB 3) is provided in the illumination beam path (1) of the ophthalmoscope, through which the observable eye fundus (10) is only partially illuminated and that an insertable fourth field stop (FB 4) is provided in the measuring beam path (2) of the ophthalmoscope, which is only transparent to the light from the unilluminated part of the eye fundus (10) to be measured as stray light .

1 1. Device according to claim 10, characterized in that the third field stop (FB 3) is designed so that the unilluminated area of the fundus (10) is the macular area and that the fourth field stop (FB 4) is aligned so that it is only permeable to light from the unilluminated macular area.

12. The device according to claim 10, characterized in that the third field stop (FB 3) limits the illumination field at the back of the eye (10) centrally around the macula with an inner diameter of 1.2 PD and with an outer diameter of 2.4 PD and that fourth field stop (FB 4) is transparent to light from a circular, unilluminated area of the fundus (10) with the inner diameter of preferably 0.4 PD.

13. The device according to claim 10, characterized in that the third and fourth field diaphragm (FB 3, FB 4) are each arranged to be pivotable into the illumination or measuring beam path (1, 2).

14. The device according to claim 10, characterized in that the second and fourth field diaphragm (FB 2, FB 4) are designed as a single diaphragm with a variable free diameter.

15. The device according to claim 10, characterized in that the third field stop (FB 3) is designed such that it only shades the macular area of the fundus (10) in a circular manner.

16. The device according to claim 10, characterized in that the field stop (FB 1) in the illumination beam path (1) of the ophthalmoscope is designed such that a part of the observable eye fundus (10) is not illuminated and that the field stop (FB 2) is designed in this way is that through this both the remitted light from the illuminated and unilluminated fundus (10) reaches the detector (13).